肿瘤核酸疫苗研究进展

基因疫苗是当前疫苗研究领域中的热点之一。肿瘤核酸疫苗主要包括与肿瘤相关抗原有关的全长、表位、独特型和融合脱氧核糖核酸疫苗,能够自主复制的核糖核酸疫苗,与树突细胞相关的肿瘤基因疫苗等。现对肿瘤核酸疫苗的研究进展进行综述。     

肿瘤免疫治疗近5年研究进展

肿瘤的免疲治疗机制是通过调动机体的天然防卫机制或给予靶向性很强的物质来取得抗肿瘤效应.在肺癌的免疫治疗中,肿瘤疫苗具有很好前景,如EGFR疫苗、MAGE-A3疫苗和针对肿瘤细胞表面表达的MUC1生产的L-BLP25等.Catumaxomab三功能抗体和Anti-p185HEH-2-RTA等在对抗胃癌中的治疗过程中也取得...     

HPV-16,-18型致宫颈癌机制及其疫苗研究

宫颈癌病例中,人乳头瘤病毒16(HPV-16),-18型的检出率可高达50%～70%.HPV-16,-18型诱发宫颈癌的主要机制是其E6和E7基因在宫颈细胞中表达增加,其基因产物E6和E7两个癌蛋白分别与抑癌蛋白P53和pRb结合,进而诱导P53和PRb蛋白降解.HPV疫苗包括预防性和治疗性疫苗.国际上预防性疫苗只有GSK的Cervarix疫苗和Merke公司的Gardsil疫苗,主要预防HPV-16,-18型感染以及HPV-16,-18型相关性宫颈肿瘤和生殖器疣的发生.预防性疫苗是通过细胞免疫和体液免疫以去除或减少已经被感染的细胞或肿瘤细胞,其靶蛋白主要为E6或E7.到目前为止治疗性疫苗的类型虽然很多,主要包括肽类疫苗、病毒载体疫苗及DNA疫苗等.因为治疗性疫苗的机制比较复杂,目前还在实验阶段.     

肿瘤患者接种流感疫苗和肺炎球菌疫苗及新型冠状病毒疫苗的研究进展

对近年来国内外肿瘤患者接种流感疫苗、肺炎球菌疫苗和新型冠状病毒疫苗的免疫原性、安全性和有效性等相关研究进行分析。通过对检索文献进行梳理和分析, 结果显示, 接种流感疫苗和肺炎球菌疫苗可显著降低肿瘤患者的感染性疾病的发病率、住院率, 还可降低其心血管事件风险和死亡风险, 显著改善生存预后。接种新型冠状病毒疫苗亦可对肿瘤患者起到保护作用, 尤其是完成全程疫苗接种的患者。国内外权威学会指南、共识均建议肿瘤患者接种流感疫苗、肺炎球菌疫苗和新型冠状病毒疫苗。建议积极开展相关研究, 并采取有效措施加强患者教育, 让肿瘤患者充分获得疫苗给这个特殊群体带来的健康保护。     

自扩增RNA疫苗研究进展

自扩增RNA(self-amplifying RNA, saRNA)疫苗为新一代mRNA疫苗，除含有编码抗原蛋白的mRNA序列外，还具有独特的自扩增元件，因此可在体内进行抗原序列的自我扩增。近年来，mRNA疫苗技术正快速发展并日趋成熟，在传染病和肿瘤等疾病中的应用不断增多，同时基于mRNA疫苗技术衍生出的saRNA疫苗在传染病和肿瘤的预防和治疗中的研究越来越备受关注，现有的研究结果也显示其巨大的发展空间，或对mRNA疫苗的研发应用产生实质性的影响。本文就saRNA疫苗的结构特点、生物学机制、递送原理和材料及在传染病、肿瘤和临床等领域的研究进展作一概述。     

妊娠期妇女新型冠状病毒疫苗接种的研究现状

2020年3月,WHO正式认定新型冠状病毒肺炎成为全球性大流行病。疫苗接种是控制这一大流行病的关键。目前研发的疫苗几乎涵盖了疫苗研究的所有类型,包括核酸疫苗、病毒载体疫苗、重组蛋白疫苗和灭活疫苗等类型。本文就孕产妇新型冠状病毒疫苗接种现状、已获得WHO许可紧急使用疫苗的类型、主要成分、作用机制、安全性和有效性评估证据、对妊娠期妇女的推荐建议,以及不同国家关于妊娠期妇女新型冠状病毒疫苗接种的相关推荐意见等方面进行综述,为后续研究及推荐指南的更新提供参考。     

新城疫病毒膜融合脂质体疫苗抑瘤的实验研究

[目的]用新城疫病毒(Newcastle disease virus,NDV)Ⅳ系弱毒株构建新型膜融合脂质体,并用此载体制备Hep-A22肝腹水瘤疫苗,免疫小鼠并考查疫苗的效应. [方法]用NDV制备膜融合脂质体,包封肿瘤抗原制成疫苗.体外观察NDV膜融合脂质体诱导的细胞毒性T淋巴细胞(CTL)反应活性及体内抑瘤效应. [结果]游离蛋白抗原不能诱发细胞毒T淋巴细胞反应;以膜融合脂质体为载体的疫苗可产生强烈的CIL反应(P＜0.001),且作用强于NDV与游离蛋白混合液的肿瘤抑制作用. [结论]用NDV构建的膜融合脂质体是一种有效的肿瘤疫苗载体.     

多肽疫苗研究进展

多肽疫苗是新一代疫苗研究的热点之一。与其他类型疫苗相比,多肽疫苗优势在于具有免疫应答能力、安全、反应原性低等。目前有包括抗病毒、抗癌、抗疟及避孕等多种多肽疫苗正在进行各期临床试验。     

乙型肝炎疫苗免疫研究进展

乙型肝炎(乙肝)疫苗自20世纪80年代问世以来,逐渐在世界各国得到广泛应用,由最初采用乙肝血源疫苗逐渐过渡到基因重组疫苗(酵母和CHO基因重组疫苗),以及各种类型的联合疫苗.应用不同类型和剂量的乙肝疫苗在各种人群中的免疫效果研究证实,该疫苗具有良好的免疫原性和保护效果.以下对乙肝疫苗控制HBV感染所取得的成效,以及对免疫应答和加强免疫等方面主要研究进展简要综述.     

关于疫苗你了解多少?

近日,接种疫苗成了热点话题,例如常见疫苗有哪些类型,疫苗的安全性如何,开发疫苗有哪些新技术等.带着上述这些问题,我们一起来了解一下关于疫苗的那些事. 疫苗的机制就是要通过自身来触发机体的免疫系统,使其产生独特的抵抗力可以抵抗外来特定病原体的入侵.对于多数传染病,一旦感染,并从感染康复后就可以在一定的时间内不再罹患同样的...     

Vaccines of the future

Vaccines of the future can be divided into three broad groups, namely those of the near future (<10 years); the medium-term future (10-19 years); and the long-term future (20-50 years). For the near future, there is some "low hanging fruit" which is clearly on the horizon, such as a Vi-conjugate vaccine for typhoid or a protein-based vaccine for Neisseria meningitidis serogroup B. Just slightly more distant will be vaccines for shigellosis and a common protein vaccine for Streptococcus pneumoniae. Also in this group, but not as far advanced, will be a vaccine for Group A streptococcus. I place vaccines for the "big three", malaria, tuberculosis and HIV/AIDS in the medium term basket. The sporozoite malaria vaccine RTS-S is closest, but surely a definitive malaria vaccine will also require antigens from other stages of the life cycle. A tuberculosis vaccine will be either a re-engineered BCG; or a molecular vaccine with several protein antigens; or one based on prime-boost strategies. What will delay this is the high cost of clinical trials. For HIV/AIDS, the partial success of the Sanofi-Pasteur prime-boost vaccine has given some hope. I still place much faith in antibody-based vaccines and especially on mimotopes of the env transitional state assumed after initial CD4 binding. Monoclonal antibodies are also leading us in interesting directions. Longer term, the vaccine approach will be successful for autoimmune diseases, e.g. juvenile diabetes and coeliac disease. Cancer vaccines are also briefly surveyed. Adjunct issues needing to be addressed include more extensive combinations; alternate delivery systems; and more intelligently designed adjuvants based on knowledge of the innate immune system.     

Comparison of the effectiveness and duration of anti-RBD SARS-CoV-2 IgG antibody response between different types of vaccines: Implications for vaccine strategies

Background and objectivesLittle is known about the efficacy and durability of anti-RBD IgG antibodies induced by certain SARS-CoV-2 vaccines. It has been shown that neutralizing antibodies are associated with the protection against re-infection. This study aims to compare the mean titers, duration, and efficacy of generating protective anti-RBD IgG antibody response among recipients of Pfizer/BioNTech, AstraZeneca, Sputnik V, Johnson & Johnson, Moderna, and Sinopharm COVID-19 vaccines. In addition, we aimed to compare the susceptibility of getting COVID-19 breakthrough infections after various types of vaccines.Materials and methodsSamples from 2065 blood bank donors and healthcare workers at King Hussein Cancer Center (KHCC) were collected between February and September 2021. Anti-Spike/RBD IgG levels were measured using Chemiluminescent microparticle-immunoassay (CMIA) (ARCHITECT IgG II Quant test, Abbott, USA).ResultsThe mean titer of anti-RBD IgG levels was significantly diverse among different types of vaccines. The highest titer level was seen in participants who took a third booster vaccine shot, followed by Pfizer/BioNTech, AstraZeneca, and Sinopharm vaccine. The mean titer levels of anti-RBD IgG antibodies in the Pfizer vaccinated group was the highest after vaccination but started to drop after 60 days from vaccination unlike AstraZeneca and Sinopharm vaccine-induced antibodies where the mean titers continued to be stable until 120 days but their levels were significantly lower. Most of the breakthrough infections were among the Sinopharm vaccinated group and these breakthroughs happened at random times for the three main types of vaccines.ConclusionsOur data demonstrate that the mean-titer of anti-RBD IgG levels drop after four months which is the best time to take the additional booster shot from a more potent vaccine type such as mRNA vaccines that might be needed in Jordan and worldwide.     

Characterization of tumor vaccines during product development

The term tumor vaccines encompasses a wide variety of diverse agents capable of interacting with the immune system to produce local inflammation, delayed type hypersensitivity reaction and/or tumor regression and, hopefully, a therapeutic effect. These vaccines may be grouped into the following general areas: (1) Cell-based vaccines such as manipulated tumor cells, activated peripheral blood or bone marrow-derived lymphocytes, dendritic cells or other antigen presenting cells (APC) and gene-modified tumor cells or other cells engineered to express cytokines, growth factors or tumor antigens. (2) Antigen preparations, such as synthetic peptides, purified antigens and tumor cell lysates. (3) Viral and plasmid vectors expressing therapeutic genes. (4) Liposome containing antigen, peptides, plasmids encoding tumor antigens. While no tumor vaccine has been licensed by the FDA, numerous clinical trials are ongoing and some products have advanced to Phase III pivotal stages of development. However, as with many novel products, major regulatory and scientific issues associated with clinical use of tumor vaccines remain to be addressed. In this paper, we address issues associated with different types of tumor vaccines and provide recommendations for the characterization of these vaccines at various stages of development.     

Using Monte Carlo Simulation to Determine Combination Vaccine Price Distributions for Childhood Diseases

The Recommended Childhood Immunization Schedule provides guidelines that allow pediatricians to administer childhood vaccines in an efficient and effective manner. Research by vaccine manufacturers has resulted in the development of new vaccines that protect against a growing number of diseases. This has created a dilemma for how to insert such new vaccines into an already crowded immunization schedule, and prompted vaccine manufacturers to develop vaccine products that combine several individual vaccines into a single injection. Such combination vaccines permit new vaccines to be inserted into the immunization schedule without requiring children to be exposed to an unacceptable number of injections during a single clinic visit. Given this advantage, combination vaccines merit an economic premium. The purpose of this paper is to describe how Monte Carlo simulation can be used to assess and quantify this premium by studying four combination vaccines that may become available for distribution within the United States. Each combination vaccine is added to twelve licensed vaccine products for six childhood diseases (diphtheria, tetanus, pertussis, haemophilus influenzae type B, hepatitis B, and polio). Monte Carlo simulation with an integer programming model is used to determine the (maximal) inclusion price distribution of four combination vaccines, by randomizing the cost of an injection. The results of this study suggest that combination vaccines warrant price premiums based on the cost assigned to administering an injection, and that further developments and innovations in this area by vaccine manufacturers may provide significant economic and societal benefits.     

Trivalent Human Papillomavirus (HPV) VLP vaccine covering HPV type 58 can elicit high level of humoral immunity but also induce immune interference among component types

Both Human Papillomavirus (HPV) type 16/18 bivalent vaccine and type 16/18/6/11 quadrivalent vaccine have been proved to be safe and effective, and licensed for public use. However, these two vaccines do not quite match the distribution of HPV types in China, Southeast Asia and Latin America, where HPV 58 is highly prevalent. Here we produced three types of virus-like particles (VLPs) in baculovirus expression system, formulated a trivalent vaccine containing HPV 16, 18, and 58 L1 VLPs and examined its in vitro neutralizing titers. This vaccine could induce high level and long-term humoral immunity against the component types. But immune interference was observed when comparing type specific neutralizing antibody levels induced by trivalent vaccine to those by corresponding monovalent vaccines. This kind of interference would become more obvious when formulating more types of VLPs into multivalent vaccines, but could be greatly overcome by decreasing the antigen dosage and adding a proper adjuvant.     

预防甲型肝炎的疫苗及其比较

目前应用的预防甲型肝炎(甲肝)的疫苗有两种:甲肝减毒活疫苗和甲肝灭活疫苗。该文评价了上述两种甲肝疫苗,并从下列四个方面进行了比较:疫苗的安全性,疫苗的免疫原性和免疫效果,疫苗保护的持久性和预防的价格-效益比。结果指出两种甲肝疫苗各有不同的优点和缺点。为预防和控制甲肝流行为主,建立群体免疫屏障,甲肝减毒活疫苗有更多的优势。这与世界卫生组织专家建议在经济欠发达国家和地区,应推广使用甲肝减毒活疫苗的意见相一致。     

Potent tetravalent replicon vaccines against botulinum neurotoxins using DNA-based Semliki Forest virus replicon vectors

Human botulism is commonly associated with botulinum neurotoxin (BoNT) serotypes A, B, E and F. This suggests that the greatest need is for a tetravalent vaccine that provides protection against all four of these serotypes. In current study, we investigated the feasibility of generating several tetravalent vaccines that protected mice against the four serotypes. Firstly, monovalent replicon vaccine against BoNT induced better antibody response and protection than that of corresponding conventional DNA vaccine. Secondly, dual-expression DNA replicon pSCARSE/FHc or replicon particle VRP-E/FHc vaccine was well resistant to the challenge of BoNT/E and BoNT/F mixture as a combination vaccine composed of two monovalent replicon vaccines. Finally, the dual-expression DNA replicon or replicon particle tetravalent vaccine could simultaneously and effectively neutralize and protect the four BoNT serotypes. Protection correlated directly with serum ELISA titers and neutralization antibody levels to BoNTs. Therefore, replicon-based DNA or particle might be effective vector to develop BoNT vaccines, which might be more desirable for use in clinical application than the conventional DNA vaccines. Our studies demonstrate the utility of combining dual-expression DNA replicon or replicon particle vaccines into multi-agent formulations as potent tetravalent vaccines for eliciting protective responses to four serotypes of BoNTs.     

考虑间接效应估计的疫苗现场试验设计

多数疫苗在人群中使用后会产生直接效应和间接效应,除接种者得到保护外,项目实施人群中的未种者也能因此受益.而传统的疫苗临床试验设计,采用个体随机化分组方式,由于不能对间接效应进行定量估计,干预措施的成本效益往往被低估.文中介绍Halloran等构建的包含间接效应估计的干预试验设计框架,提供包括直接效应、间接效应、总效应和整体效应等指标的计算方法,并阐述各类效应的意义及其相互关系,结合在孟加拉国开展的口服霍乱疫苗和在印度开展的伤寒vi疫苗两个现场试验实例,对间接效应的识别及其实际应用价值等内容作进一步探讨,为研究人员设计疫苗现场试验方案提供参考.

Abstract：

For most variety of vaccines, two types of effects-direct and indirect, can result from immunization programs. Unimmunized individuals in the population that receive immunization program can benefit from the vaccines in addition to the protection from immunization.The classical vaccine trails allocate individuals into study and control arms with individual randomization, so the programs' cost-benefit is underestimated due to the impossible measurement on indirect effect. The objectives of the present work are to introduce the conceptual framework,developed by Halloran et al, for four types of study designs that differentiate and account for direct,indirect, total and overall effects of intervention programs, and to explain the relationships of these effects as well. With the examples of field trails of oral cholera vaccines in Bangladesh and Vi typhoid vaccine in India, further issues refer to the identification of indirect effect. The application in practice is also discussed.     

乙型肝炎疫苗与婴儿期常用疫苗同时接种的免疫应答与反应观察:Ⅰ.乙型肝炎疫苗与白百破混合疫苗、脊髓灰质炎活疫苗同时接种的免疫应答与反应观察

本文对HB疫苗与DPT、TOPV疫苗同时接种的免疫应答性作了研究。对0~5月龄的229名婴儿随机分为Ⅰ组单独接种HB疫苗,Ⅱ组接种DPT、TOPV疫苗,Ⅲ组HB疫苗与DPT、TOPV同时接种。三针间隔为0、1、5个月,均作免前和第三针后一个月的血清抗体测定,同时接种组的抗-HBs、白喉、破伤风、百日咳及Ⅰ、Ⅱ、Ⅲ型OPV抗体的阳转率、GMT与单独接种组无差别。未见异常反应,一般反应均很轻微,二组间无差别。表明上述几种疫苗同时接种是安全和有效的。     

A controlled field trial of the effectiveness of monovalent classical and El Tor cholera vaccines in the Philippines

Monovalent Ogawa and Inaba vaccines prepared from classical and El Tor strains of Vibrio cholerae were field-tested in Negros Occidental, Philippines, where cholera El Tor, serotype Ogawa, is endemic. The monovalent classical Ogawa and Inaba vaccines were of the same lots as those tested in East Pakistan in 1968-69. The results indicated that all four types of vaccine tested offered significant degrees of protection varying from 58% to 71%. The Ogawa vaccines were slightly, though not significantly, more protective than the Inaba vaccines against disease caused by Ogawa. The biotypes of the vaccine strains were found to be of no consequence.